The incidence of diabetic nephropathy and cardiovascular disease among Minnesota American Indians with non-insulin dependent diabetes mellitus (NIDDM) is high and growing at an alarming rate. Unfortunately, few data are available to suggest the best therapy for preventing complications of NIDDM. We have developed a partnership between American Indians, Indian Health Service personnel, and clinical investigators to address this problem at the Red Lake and Leech Lake reservations in Northern Minnesota. We propose a clinical trial that will provide intensive therapy for all participants, including diet, exercise, smoking cessation, blood pressure reduction, and cholesterol reduction. This trial will examine two important questions: 1) whether angiotensin converting enzyme inhibitors or calcium channel blockers differ in their effectiveness; and 2) whether a more aggressive lipid lowering strategy than that currently recommended by the National Cholesterol Education Program is beneficial. Specifically, we will use microalbuminuria to target a high risk population of NIDDM patients. We will invite these patients to participate in a pilot study that will use a therapeutically-focused, 2 X 2 factorial design to examine the independent and interactive effects of different blood pressure and lipid reduction strategies. We will examine the effects of these strategies on changes in glomerular filtration rate, albuminuria, blood pressure, serum lipoproteins and other parameters. The information and experience we gain from this pilot project will ultimately allow us to carry out a larger, multi-reservation study aimed at preventing the devastating complications of NIDDM among American Indians.